Recently the trend toward natural products of people has been rising, and in the field of the fragrance, there also arouses an interest for a musk-feeling fragrance having a higher aroma property and characteristically reminding of natural environment. Further, there is also a need for development of a new fragrance material derived from a natural compound or the same as or similar to a natural compound, from the point of safety for human beings and the environment.
Muscone is the principal fragrance component in natural musk and contained in the amount of 0.5 to 2.0% therein. Muscone was found out by Walbaum in 1906, and its chemical structure was determined by Ruzicka in 1926. Natural muscone is (−)-(R)-3-methylcyclopentadecanone, but its commercial product is a synthetic dl-isomer. When the fragrance of (−)-(R)-isomer and (+)-(S)-isomer is compared, the (R)-isomer has a diffusive stronger musk-feeling fragrance (threshold value: 3 ppm), while the (S)-isomer has a chemical, less-diffusive, poor and weak musk-feeling fragrance (threshold value: 10 ppm), and thus, the intensity of the fragrance of the (R)-isomer is known to be thrice greater than that of the (S)-isomer (see, for example, Non-patent Document 1 and Non-patent Document 2 below).
Non-patent Document 1: Indo Motoichi, “Synthetic Aromachemical—Chemistry and Commodity knowledge”, The Chemical Daily, Mar. 6, 1996, pp. 492 to 497.
Non-patent Document 2: “Recently technology on Synthetic Aromachemical”, CMC Publishing, 1982, pp. 72 to 90.
For the reasons above, there have been many reports of the studies on the method of preparing muscone, in particular, (−)-(R)-muscone. Among them, a method of producing an optically active muscone by 1,4-conjugation methyl-addition reaction of 2-cyclopentadecenone is considered to be promising, and there are recently some reports on the methods of preparing (−)-(R)-muscone in asymmetric methylation reaction using an optically active ligand. For example, it has been reported that it is possible to obtain favorable results by using a compound having an amino alcohol chiral auxiliary group containing a bornane skeleton in preparation (see Non-patent Document 3 below). However, the reported method of producing the (−)-(R)-muscone by using a chiral auxiliary group is yet to be commercialized, because it has disadvantages of demanding an extremely low reaction temperature of −78° C., an extended reaction time, and use of a chiral auxiliary group in an excessive amount of one equivalence or more. In another example, there is a report that a particular chiral phosphite compound gave a favorable result when various chiral phosphite ligands were examined in a catalytic amount (see Non-patent Document 4 below). However, the reported method shows a yield of 53% even at an inefficiently low concentration at a solvent/substrate rate of approximately 50 and thus, is not desirable. In yet another example, described is high-yield production of muscone by using a copper complex of 4-(cis-2,6-dimethylpiperidine) -(R)-dinaphthodioxaphosphepin or 4-(R,R-2,5-diphenyl-pyrrolidine) -(R)-dinaphthodioxaphosphepin as a chiral ligand (see Patent Document 1 below), but the literature does not disclose the reaction at higher concentration. When the reaction is carried out at higher concentration, conventional methods cause a problem of poor yield of the objective product by generation of high-molecular weight by-products. Further, the employment of an extreme reaction condition such as an extremely low temperature, a low concentration or an extended reaction period results in increase of a production cost. Low reaction yield also leads to increase of a production cost. Therefore, there exists an urgent need for a method of producing muscone economically at high yield without employing a reaction condition such as an extremely low temperature, a low concentration, or an extended reaction period.
Non-patent Document 3: J. Chem. Soc. Perkin Trans. I, 1193 (1992)
Non-patent Document 4: Synlett 1999, No. 11, pp. 1181-1183
Patent Document 1: Korean Patent Application Laid-Open No. 2001-49811